Actual Eye Pharmacology

Question 1

Durgs we are dealing with in occular pharmacology

Answer 1

1. Drugs that cause mydriasis (pupil dilation)
2. Inc tear production
3. Tear substitutes
4. Glaucoma treatments

Question 2

What is glaucoma?

Answer 2

• Sustained increase in intraocular pressure (IOP) usually due to reduced aqueous humour outflow (diff to humans)
o Can lead to pain, blindness, irreversible changes to eye structure
• Chronic low grade inflammation

Question 3

What is the aim of treatment with glaucoma

Answer 3

o Inc outflow aq humour
o Dec production aq humour
o Combine both (usually combo as hard to treat!)

Question 4

What drug would you sue to treat glaucoma if caught early

Answer 4

• Osmotic diuretics
o first-line treatment in an acute presentation if caught early - increase in blood tonicity causes water to be drawn out of the aqueous and vitreous.
o This relies on an intact BOB
o Short-acting
o Cannot be safely used repeatedly due to the risk of hypovolaemia, volume depletion (emergency intervention only)

Question 5

Other than osmotic diuretcs, list the other drugs used to treat glaucoma

Answer 5

• Carbonic anhydrase inhibitors (CAIs) e.g. brinzolamide and dorzolamide
• Prostaglandin analogues e.g. latanoprost
• Beta-blockers e.g. betaxolol
• Direct Parasympathomimetics e.g. pilocarpine

Question 6

Carbonic anhydrase inhibitors (CAIs) and glaucoma

Answer 6

o MOA: Carbonic anhydrase catalyses the reversible hydration of CO2 to HCO3- + H+ in the non-pigmented ciliary body epithelium
o bicarbonate ions moves ions into the aqueous humour drawing water into the aqueous humour (active transport)
o inhibition of this will reduce aqueous humour production.
o brinzolamide and dorzolamide penetrate the eye and achieve therapeutic levels in the ciliary body to give similar efficacy

Question 7

Prostaglandin analogues and glaucoma

Answer 7

o MOA: increases uveoscleral outflow of aqueous humour, due to alteration in the ultrastructure of the outflow tract
o thought to assist with vision preservation due to increased perfusion of the retina and optic nerve head by vasodilation of vessels
o can be irritating causing blepharospasm, epiphora (inc watery tear film) and conjunctival hyperaemia, & darkening of the iris and periocular skin
o Latanoprost is metabolised to its active form during passage through the corneal epithelium. (pro drug)

Question 8

Beta blockers and glaucoma

Answer 8

o reduce aqueous humour formation by uncertain mechanisms e.g. blockade of β receptors in the ciliary body, inhibition of Na/K ATPase and vasoactive actions (theories)
o betaxolol is a topical β1-selective agent which has also been shown to be neuroprotective due to its effect on ion channels

Question 9

Direct parasympathomimetics and glaucoma

Answer 9

o MOA: contraction of ciliary body and constriction of the pupil, widens the drainage angle for aq humour & increases outflow of aqueous humour
o only effective if the drainage apparatus is intact, which it often is not in veterinary glaucoma patients
o must have a functional drainage apparatus – often don’t work v well
o Stimulates tear production, has other effects so not often used for this purpose
• Indirect parasympathomimetics (acetylcholinesterase inhibitors) not often used due to the higher risk of side effects & ocular irritation. Can get GI side effects.

Question 10

What are the different tear substitute categories?

Answer 10

3 different categories, each mimicking one of the components of the tear film: Aqueous substitutes, mucin and lipid replacements

Question 11

• Aqueous substitutes

Answer 11

o lost quickly from the ocular surface so usefulness is limited without additives to prolong their retention
o require extremely frequent administration to be useful in KCS (keraticinjunctivitis Sicca).
o Don’t tend to use

Question 12

• Mucin Replacements

Answer 12

o Carbomer gel
 mimics the mucin layer of the tear film
o hyaluronic acid containing drops (topical viscous gel)
 more effective in controlling the discomfort and inflammation associated with dry eyes
 Products with cross linked hyaluronic acid are more effective due to their increased visco-elastic properties & bioadhesion

Question 13

Lipid Replacements

Answer 13

o replace the lipid portion of the tear film (meibomium gland), aiming to increase retention of the tear substitute (reduce evaporation) and extend its duration of action. These are in the form of lipid emulsions. As addition to tear substitute to keep tear in eye for longer
• Intraocular bioavailability of topically applied drugs can be improved by increasing retention of drug in palpebral fissure

Question 14

What are the 2 categories of drugs that cause Mydriasis

Answer 14

(pupil dilation)
It is often desirable to dilate the pupil to facilitate better fundic examination. Given the physiology of iris control, drugs which achieve this must be either parasympatholytics, which act to relax the iris sphincter muscle causing dilation, or sympathomimetics, which contract the dilator muscle.

Question 15

List Drugs that cause mydriasis

Answer 15

• Atropine (parasympatholytic
• Tropicamide (parasympatholytic
• Phenylephrine (Sympathomimetics

Question 16

Atropine

Answer 16

Causes mydriasis via parasympatholytics = acts to relax the iris sphincter

o slow onset, long duration, useful for inducing cycloplegia (relax ciliary body when spasming if painful) in uveitis since, once dilation & relaxation have been achieved (which is after about 1 hour in the normal eye but variable in the inflamed eye), the effect can last up to 120 hours
o bitter tasting (hypersalovating), induces salivation, can cause systemic antimuscarinic effects - problematic in the horse (colic) so use carefully

Question 17

Tropicamide

Answer 17

Causes mydriasis via parasympatholytics = acts to relax the iris sphincter

o much faster (within 30 minutes) and shorter acting (8-12 hours) antimuscarinic drug
o useful for dilation of the pupil for examination purposes

Question 18

• Phenylephrine

Answer 18

Sympathomimetics - contract the dilator muscle for mydriasis

o α1-selective adrenergic drug which acts within 10 minutes of application
o used in horner’s syndrome

Only ocular mydriasis S)

Question 19

2 categoreis of drug that inc tear production

Answer 19

• Parasympathomimetic actively inc tear production e.g. pilocarpine
• Immunosuppressant actively inc tear production e.g. ciclosporin, marketed as Optimmune® eye:
o Ointment licensed for first line treatment of Keratoconjunctivitis Sicca (immune-mediated disease of the lacrimal glands). This is the first line treatment under the prescribing cascade.